William Panenka

Background: Advanced magnetic resonance imaging (MRI) techniques, including diffusion tensor imaging (DTI) and myelin water imaging (MWI), are commonly used to assess the white matter (WM) architecture in the brain. These techniques have been used to evaluate the WM alterations incurred following mild traumatic brain injury (mTBI), however they are currently not sensitive or specific enough for routine clinical use. The corpus callosum (CC) is the WM pathway most susceptible to damage from mTBI. Objectives: The primary objective of this thesis was to investigate the sensitivity of DTI and MWI to the microstructural changes incurred after mTBI in the CC, at 2 weeks (2W) and 6 months (6M) post-injury, and to assess how imaging metrics changed over the time period from 2W to 6M. Secondary exploratory analyses were completed to investigate (i) the associations of MWI and DTI imaging metrics with day of injury (DOI) characteristics of injury severity, such as presence of loss of consciousness (LOC+) and trauma-related findings on DOI computed tomography scans (CT+) (ii) group differences in these imaging metrics in other regions commonly injured after mTBI, and (iii) group differences in neuropsychological (NP) scores and their potential correlation to imaging metrics. Participants and Methods: The data was collected as part of an imaging sub-study to the Canadian Traumatic Brain Injury Project (CanTBI). Tract based spatial statistics (TBSS) was used to analyze the DTI and MWI metrics, while generalized linear modelling was used to compare group differences in the metrics. Results: There were no significant cross sectional group MWI differences between the mTBI subjects and TC controls at either time point. DTI analyses, however, revealed significantly lower fractional anisotropy and higher radial diffusivity in the mTBI subjects, in the splenium and whole CC, at both 2W and 6M. The secondary analyses revealed some interesting findings regarding the effects of DOI characteristics on imaging metrics, and the group differences in neuropsychological metrics. Conclusion: Overall, this thesis demonstrated the sensitivity of DTI to mTBI, while emphasizing the need for further validation of MWI in its diagnostic application to mTBI.

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Reductions in hippocampal volume have been well established as a correlate of disease expression in a variety of psychiatric and neurological disorders such as Alzheimer’s dementia, major depressive disorder, schizophrenia, HIV infection, traumatic brain injury (TBI), and substance abuse. Although conventional neuroimaging studies focus on the measurement of total volume as a surrogate measure for integrity, abnormalities in hippocampal morphology are intuitively equally important yet less well-studied. Hippocampal cavities (HCs) are a common morphological variant found frequently on magnetic resonance imaging (MRI) examinations of the brain. Although they are common findings, their etiology and significance are unclear. We conducted a systematic review of the risk factors for the presence and severity of HCs visualized on MRI. We found that the vascular risk factors of age and hypertension were the most robust risk variables associated with HC, but limited associative evidence exists for a diverse set of other variables including apolipoprotein E (APOE) genotype, smoking, depression, transient global amnesia, mild cognitive impairment and dementia. Considerable methodological heterogeneity is a marked limitation of the current literature. Meta-analysis confirmed the presence of significant heterogeneity between studies (I²: 95% CI [94.3%, 94.0%], p
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